التفاصيل البيبلوغرافية
| العنوان: |
The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer |
| المؤلفون: |
Evans, JP, Winiarski, BK, Sutton, PA, Jones, RP, Ressel, L, Duckworth, CA, Pritchard, DM, Lin, ZX, Vicky, FL, Tweedle, EM, Costello, E, Goldring, CE, Copple, IM, Park, BK, Palmer, DH, Kitteringham, NR |
| المصدر: |
Oncotarget |
| سنة النشر: |
2018 |
| مصطلحات موضوعية: |
respiratory system, neoplasms, digestive system, environment and public health, digestive system diseases |
| الوصف: |
© Evans et al. Nrf2 is a transcription factor that regulates cellular stress response and irinotecan-metabolising pathways. Its aberrant activity has been reported in a number of cancers, although relatively few studies have explored a role for Nrf2 in colorectal cancer (CRC). This study assessed the expression of Nrf2 in patient CRC tissues and explored the effect of Nrf2 modulation alone, or in combination with irinotecan, in human (HCT116) and murine (CT26) cell lines in vitro and in an orthotopic syngeneic mouse model utilising bioluminescent imaging. Using a tissue microarray, Nrf2 was found to be overexpressed (p < 0.01) in primary CRC and metastatic tissue relative to normal colon, with a positive correlation between Nrf2 expression in matched primary and metastatic samples. In vitro experiments in CRC cell lines revealed that Nrf2 siRNA and brusatol, which is known to inhibit Nrf2, decreased viability and sensitised cells to irinotecan toxicity. Furthermore, brusatol effectively abrogated CRC tumour growth in subcutaneously and orthotopicallyallografted mice, resulting in an average 8-fold reduction in luminescence at the study end-point (p=0.02). Our results highlight Nrf2 as a promising drug target in the treatment of CRC. |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=core_ac_uk__::c5a0f3d5005d2d5f8d85b80301049a22
http://livrepository.liverpool.ac.uk/3024449/1/25497-1005819-3-PB.pdf |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.core.ac.uk....c5a0f3d5005d2d5f8d85b80301049a22 |
| قاعدة البيانات: |
OpenAIRE |
